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Differences in neuropathologic characteristics across the Lewy body dementia spectrum

From the Wolfson Centre for Age-Related Diseases (C.B.), Wolfson Building, Guy's Campus, King's College London, UK; Institute of Ageing and Health (I.Z., R.P., J.O., I.M., E.P.), Newcastle General Hospital, Newcastle upon Tyne, UK; and Norwegian Center for Movement Disorders (J.P.L., D.A.), Stavanger University Hospital, Stavanger, Norway.

Address correspondence and reprint requests to Dr. Ballard, Wolfson Centre for Age-Related Diseases, Wolfson Building, Guy's Campus, King's College London, London, SE1 1UL, UK; e-mail: clive.ballard{at}kcl.ac.uk

Background: The objective of this comparative neuropathologic study was to determine the extent to which dementia with Lewy bodies (DLB) and Parkinson disease dementia (PDD) are distinct entities or part of a continuum with respect to the duration of parkinsonism.

Methods: We evaluated the relationship between cortical -synuclein pathology, plaques (Consortium to Establish a Registry for Alzheimer's Disease [CERAD]), tangles (Braak staging), and cholinergic deficits (choline acetyltransferase in temporal cortex) in 57 prospectively assessed patients (29 DLB, 28 PDD), confirmed at autopsy. The PDD group was divided according to the median duration of parkinsonism prior to dementia.

Results: There was an association between longer duration of parkinsonism prior to dementia and less severe cortical -synuclein pathology (² 10.4, df 2, p = 0.006) and lower CERAD plaque scores (² 26.6, df 9, p = 0.002), but not Braak staging. These findings were confirmed in a further correlation analysis, which also identified an unexpected correlation between more pronounced cortical cholinergic deficits and longer duration of parkinsonism prior to dementia (R = –0.37, p = 0.04).

Conclusion: While there is a clear relationship between the duration of Parkinson disease prior to the onset of dementia and key neuropathologic and neurochemical characteristics, there is a gradation of these differences across the dementia with Lewy bodies/Parkinson disease dementia spectrum and the findings do not support an arbitrary cut-off between the two disorders.

Editorial, see page 1910

Supported by the Norwegian Medical Research Council (clinical and neuropathologic assessments of the Stavanger cohort and neurochemical assessments) and the Medical Research Council UK (clinical and neuropathologic assessments of the Newcastle cohort).

Disclosure: The authors report no conflicts of interest.

Received January 26, 2006. Accepted in final form September 21, 2006.

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